#90424: Seizures and Epilepsy Syndromes

In the mid-1800s, a seizure was described as an abnormal electrical discharge of the brain [1]. This description continues to typify our conceptualization of the definition of seizures. A seizure is a finite event of altered cerebral function because of excessive and abnormal electrical discharges of the brain cells [2]. This activity can interrupt the ongoing mental and behavioral activities of the individual. In general, a seizure is characterized by a transient alteration in cognizance and/or control over physical processes [2]. The alterations in brain activity occur suddenly. These disturbances may cause changes in awareness, bodily movements, sensations, and/or emotions [3].

A seizure may be a symptom of central nervous system (CNS) irritability due to a non-neurologic disorder or medical illness. There are many examples of these extra-cranial disorders, including: metabolic disturbances or disorders (e.g., diabetes); substance abuse; dehydration and water intoxication; liver, kidney, cardiac, or pulmonary disease; hypertension; septicemia; fever; and trauma [4]. If a seizure ceases when the systemic or metabolic condition is corrected, it may be considered a symptom of the underlying disorder. In these cases, the patient is not considered to have epilepsy.

The word epilepsy is derived from the Greek word epilambanein, meaning to attack or seize [3]. Conceptually, epilepsy is defined as "a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychologic, and social consequences of this condition" [5]. An isolated seizure does not indicate epilepsy. Approximately 7% to 8% of American adults will experience a seizure in their lifetime [2]. The majority of these seizures, however, are attributable to a specific cause, such as those mentioned above. Epilepsy, in contrast, is a recurrent illness [3]. It is a paroxysmal neurologic disorder consisting of recurrent episodes of alterations in level of consciousness, convulsive movements or other motor activity, sensory phenomena, behavioral abnormalities, and mental impairment. In clinical practice, epilepsy is considered to be present if any of the following conditions are present [6]:

Epilepsy is considered to be resolved for individuals who had age-dependent epilepsy syndrome but are now past the applicable age or those who have remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years [6].

Unfortunately, the word "epilepsy" is often inappropriately used as a generic term to describe disorders in which patients experience seizures. Compared to the 7% to 8% of Americans who will experience a seizure event in their lifetime, less than 2% of the adult population will be diagnosed with epilepsy [2,7].

Epilepsy is the fourth most common neurologic disorder in the United States, after migraine, stroke, and Alzheimer disease [11,12]. Active epilepsy affects 3 million American adults, or approximately 1.2% of the U.S. population, and nearly 470,000 children (0 to 17 years of age) [13,14,15]. However, the incidence of active epilepsy is 1.9% among adults with annual family incomes less than $34,999 and 0.2% among adults with annual family incomes greater than $100,000. An estimated 150,000 new cases of epilepsy are diagnosed in the United States each year [12,16].

One in 100 individuals will be diagnosed with epilepsy before 20 years of age [11]. By 75 years of age, roughly 2% of individuals will have active epilepsy and 7% to 10% will have experienced a seizure. New cases of the disorder are most common in individuals younger than 1 year of age and older than 55 years of age, largely because risk factors are highest in these age-groups [14]. In infants, birth injuries, high fevers, temporary metabolic abnormalities (e.g., abnormal blood sugar levels), brain disorders, and congenital defects are the primary causes of epilepsy. From 2 to 20 years of age, the cause is often unknown. After 25 years of age, brain tumors, other structural lesions, and alcohol withdrawal are the foremost contributing causes; however, in about half of this population, the cause is unknown [4]. Stroke is the cause of 50% of all seizures and 30% to 50% of epilepsy in elderly adults [17].

Epilepsy is more likely to occur in certain populations, and there does appear to be some genetic influence. High-risk populations include [12]:

The financial issues associated with the care of patients with epilepsy are far reaching. Considerations include reduced income due to the loss of work and increased long-term medical expenses. The direct annual medical care costs of epilepsy in the United States are estimated to be $18.5 billion to $25 billion [18]. Medical costs include office visits, medications, and diagnostic studies. Findings from studies, presented to the American Academy of Neurology (AAN), have indicated that expenses related to other health issues (i.e., excluding epilepsy) in patients with epilepsy accounted for 80% of total annual costs for epilepsy patients [19]. Of that, 13% were attributable to mental health-related expenditures. Outpatient services accounted for 34%, inpatient services for 28%, and drugs for 27% of direct annual costs [19].

Indirect costs include the corresponding reduction in earnings from unemployment and underemployment. Epilepsy is somewhat unique in that 85% of total annual costs (direct and indirect) are productivity-related; these indirect costs are as high as $140 billion per year [18,20]. It can be a challenge for persons with epilepsy to find employment. In order to work, some patients are forced to accept positions that do not fully utilize their knowledge, skills, and abilities. Although the person with epilepsy may be a good employee and complete assigned tasks, overcoming negative attitudes may be the more daunting challenge. Advocacy efforts have begun to increase the employment and success rates for people with epilepsy in the workplace. The Americans with Disabilities Act (ADA) was enacted to prohibit disability-based discrimination. Many provisions of the ADA have particular impact on people with epilepsy, including inclusion for safety-sensitive jobs and reasonable accommodation. While many people with epilepsy are able to maintain regular employment without interruption, others may need to miss work because of seizures or changes in medication or to visit a doctor for regular monitoring. Federal laws, including the ADA and the Family and Medical Leave Act, as well as some state laws, offer employment-related protection for individuals with epilepsy [21].

The patient may require referrals to a social worker or state agency for financial support or assistance with living arrangements. These agencies may assist with job training, vocational rehabilitation, counseling, transportation, or housing. Some patients may qualify for financial support through a disability program. For example, the Ticket to Work and Work Incentives Improvement Act of 1999 was established to allow individuals with epilepsy and other disabilities to obtain employment and receive extended Medicare benefits [22]. Additional assistance may be obtained for patients through their local health departments and organizations such as the Epilepsy Foundation.

The age at which a patient first develops the seizure is often an indication of the etiology, if an identifiable etiology can be elicited. Neonates and infants often experience seizures due to perinatal injuries, hypoxia, metabolic changes, and congenital defects. Children may experience seizures due to hyperpyrexia, CNS infections, or idiopathic reasons; a primary cause of seizures is head trauma [11,24]. In adulthood, a brain mass is a common etiology. Cerebrovascular disease is the most common cause in the elderly [38,39].

The three generally recognized phases of a seizure are the prodrome (or preictal), ictal, and postictal stages [43]. Not all patients experience, nor do all seizures include, every phase. The prodromal phase can last several days preceding a seizure. The prodrome is generally characterized as malaise or emotional changes [43]. An aura occurs immediately prior to a seizure, usually lasting a few seconds. Patients often describe an aura as a warning. An aura may be autonomic or it may involve the auditory, olfactory, sensory, or visual senses. The description of an aura can vary and may include weakness, an epigastric sensation, a sense of fear, visual hallucinations, aphasia, headache, feelings of being hot or cold, or sensing unpleasant odors [43]. If a patient experiences auras (and not all do), the auras are usually fairly consistent in that individual. However, auras may vary in the same patient, and the use of antiepileptic drugs (AEDs) may alter or obscure the aura.

The ictal phase is the duration of the actual seizure activity [43]. The patient experiences a paroxysmal, uncontrolled, abnormal, and excessive discharge of electrical activity in the brain [43]. There are also corresponding EEG changes [41]. The clinical manifestations will coincide with the type of seizure activity that the patient is experiencing.

The postictal period is the interval after the seizure episode. The patient may experience some change in consciousness or behavior [43]. Some patients experience Todd paralysis, a numbness or weakness of an affected extremity or the side of the face. After a tonic-clonic seizure, the postictal phenomena may be more severe. The patient may experience amnesia, confusion, fatigue, and/or coma [41]. Often, neuronal discharges remain abnormal and the EEG may indicate some slowing.

A fourth phase recognized by some experts is the interictal phase, the period between seizures. Many people with epilepsy suffer from emotional changes during this phase, including fear, anxiety, and depression [44]. These disturbances can be more troublesome to patients than the seizures themselves.

There are several known conditions that may cause an increase in seizure activity in susceptible individuals. Sleep deprivation, mental and physical stress, acute illness, excessive fatigue, flashing lights, and hyperventilation are among the most common exacerbating factors [3,45]. The use or abuse of stimulants or alcohol also has been linked to the increase in seizure activity in sensitive individuals.

Following are the changes in seizure type classification from 1981 to 2017. Several of these changes were already incorporated into the 2010 revision of terminology [9]:

Generalized seizures begin and spread rapidly in bilaterally distributed networks and are followed by a period of postictal phase of continued altered consciousness [8,46]. They are thought to originate from structures deep within the brain, radiating outward to the cortical surface. The networks may include cortical and subcortical structures, but the entire cortex is not necessarily affected. When a generalized seizure begins, there is synchronous involvement of the entire brain with diffuse EEG abnormalities. Approximately 20% to 25% of seizures are classified as generalized at onset [41]. Generalized seizures may result in a loss of consciousness, convulsions, falls, or muscle spasms. Some generalized seizures may encompass all of these events, while others may involve only one symptom.

Generalized-onset seizures can be further classified as motor- and nonmotor-onset. Motor-onset seizures include tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, and epileptic spasms. Nonmotor-onset (absence) seizures include typical absence, atypical absence, myoclonic absence, or absence with eyelid myoclonia. Level of awareness is not used as a classifier for generalized seizures, since the large majority are associated with impaired awareness [10]. Each of these seizures occurs with a predictable pattern accompanied by distinctive differences based on the individual patient.

Focal seizures (previously referred to as "partial seizures") are the more common classification and originate in a circumscribed area or areas of the brain (i.e., a localized brain disturbance). This type of seizure occurs in 75% to 80% of patients with epilepsy [44]. Focal-onset seizures vary in terms of manifestations and severity and can result in changes in motor, sensory, and emotional functions, with or without impairment of consciousness. Focal seizures are further described according to symptoms and brain involvement [8]. Focal seizures should be classified by the earliest prominent feature (with the exception of a focal behavior arrest seizure) [10].

For focal-onset seizures, specification of the level of awareness is an optional classifier [9]. Retained awareness means that the person is aware of self and environment during the seizure, even if immobile. A "focal aware seizure" (with or without any subsequent classifiers) corresponds to the prior term "simple partial seizure." A "focal impaired awareness seizure" (with or without any subsequent classifiers) corresponds to the prior term "complex partial seizure." Impaired awareness during any part of the seizure renders it a focal impaired awareness seizure [9].

In the past, a focal seizure was considered to be complex if it included the corresponding symptom of impaired awareness or loss of consciousness [38,44]. However, the words "complex" and "simple" can be misleading in some contexts. Complex implies that this seizure type is more complicated or difficult to understand than other seizure types. Simple seems to trivialize the impact of the seizure to the patient who finds nothing simple in either the manifestations or consequences of the seizure [9]. For these reasons, "complex" and "simple" are discontinued terms in the 2017 ILAE classification scheme [9].

A focal motor seizure occurs from a focus in the region of the brain's motor cortex. Motor activity occurs in the corresponding part of the body innervated by the motor neurons that are affected. The hands and fingers have a large cortical representation; consequently, seizures are frequently noticed in these areas. The duration of these seizures is usually one to two minutes, although the patient may require additional time to completely recover after the event [4,7]. The patient will present with twitching/jerking movements in an extremity, the face, the eyes, or another area of the body. The patient remains fully conscious and aware of the seizure but has no control of the event [4]. These seizures usually remain localized, but the involuntary movement may spread centrally and involve an entire limb, one side of the body, or the entire body [4,10,44]. A Jacksonian march seizure involves the recruitment of additional muscles along the same side of the body in a progressive, step-wise fashion. The seizure may progress to involve other parts of the brain and affect other parts of the body [4].

Motor-onset focal seizure behaviors include atonic (loss of tone), tonic (sustained stiffening), clonic (rhythmic jerking), myoclonic, or focal flexion/extensions of arms and flexion of trunk (epileptic spasms). Other less obviously focal motor-onset behaviors include automatisms and hyperkinetic activity (e.g., pedaling, thrashing) [10]. Automatisms are more or less coordinated, purposeless, and repetitive motor activity and may be seen in focal seizures and in absence seizures [10]. Some automatisms overlap other motor behaviors, such as hyperkinetic activity, which renders classification ambiguous. The 2017 ILAE classification scheme arbitrarily groups pedaling activity with hyperkinetic seizures rather than with automatism seizures. Hyperkinetic seizures are a new addition to the focal seizure category.

Nonmotor-onset focal seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction [10]. Focal autonomic seizure symptoms include those consistent with involvement of the autonomic nervous system, including cardiovascular, gastrointestinal (GI), sudomotor, vasomotor, and thermoregulatory functions (e.g., changes in heart or respiratory rate, increased sweating, or unpleasant sensations in the viscera or head) [3,10,49]. Other patients may experience piloerection (goosebumps), pupillary changes, nausea, and flushing.

The dominant feature of a behavior arrest seizure (formerly "akinetic seizure") is the cessation of activity throughout the seizure, including cessation of movement (e.g., freezing, immobilization) and unresponsiveness [10]. Cognitive seizures imply impaired language or other cognitive domains or positive features (e.g., déjà vu, hallucinations, illusions, perceptual distortions). Emotional seizures involve anxiety, fear, joy, other emotions, or appearance of affect without subjective emotions [10].

A focal sensory seizure is a perceptual experience not caused by appropriate stimuli in the external environment [10]. It is usually not observable by others but may involve any of the senses [10]. Transient sensory symptoms are experienced and may involve alterations in vision, hearing, taste, touch, and smell. As with motor seizures, there is no loss of consciousness [10]. These sensory seizures may occur in the parietal, occipital, or posterior temporal lobes. The patient may describe paresthesias or numbness, tingling, bright flashing lights in vision fields, nausea, odd smells, buzzing sounds, voices, epigastric sensations, or difficulty speaking [50]. Diagnosis of this type of seizure would include specific descriptors of the sensory involvement (e.g., visual, auditory, olfactory, gustatory, epigastric) or a general descriptor (e.g., illusory experiential seizure), especially with multiple sensory involvement [50].

The events of a focal seizure have been described as follows:

The patient suddenly stopped talking and stared at the ground. Her head moved slowly to the side and she began rubbing the table with one hand, as if she was smoothing down a piece of paper. Her movements were slow and appeared deliberate. I asked the patient to remember "purple elephant." I asked the patient to lift one foot off of the floor, but there was no response. The event lasted 90 seconds. The patient moved back to her previous position in the chair with her head in a neutral position and her hand in her lap. She looked at me, with a groggy expression, and stated repeatedly, "I'm ok." The patient was slow to respond and lethargic for several minutes. After she was alert, she could not recall the event or the phrase "purple elephant." The patient complained of a headache and fatigue. After a period of rest, she was able to resume her usual activities.

Epileptic spasms are characterized by sudden flexion, extension, or mixed extension/flexion of mainly proximal and truncal muscles that is usually not so sustained as a tonic seizure but more sustained than a myoclonic movement, lasting approximately one second [49]. Epileptic spasms may occur in other forms, such as grimacing or head nodding, and they frequently occur in clusters. Spasms are most commonly observed in infants and young children, and this classification replaces the previous category of infantile spasms [10].

Unclassified seizures include both seizures with patterns that do not fit into the other categories or seizures presenting insufficient information to allow categorization. This classification is reserved for unusual events likely to be seizures but not otherwise characterized. If the seizure is unclassified because the type of onset is unknown, a limited classification may still derive from observed features [10].

There is a difference between the classification of seizure types and epileptic syndromes. Some patients with epilepsy experience one type of seizure; others experience several different seizure events. Different syndromes account for the varying patient histories, etiology of seizures, seizure type, clinical presentation, EEG readings, and neuroimaging findings. The ILAE has established an International Classification of Epilepsies and Epileptic Syndromes. The Classification was updated in a 2017 position paper to reflect the gain in understanding of the epilepsies and their underlying mechanisms. The updated epilepsies classification scheme is designed to work with the ILAE's 2017 revised seizure classification scheme [9,51]. In the 2017 epilepsies classification paper, the term "benign" is replaced by the terms "self-limited" and "pharmacoresponsive;" the term "developmental and epileptic encephalopathy" can be applied in whole or in part, where appropriate [51].

The ILAE Task Force defines an epilepsy syndrome as "a characteristic cluster of clinical and EEG features, often supported by specific etiological finds (i.e., structural, genetic, metabolic, immune, and infectious)" [51]. At its core, an epilepsy syndrome must have characteristic electroclinical features [51]. Syndromes often have age-dependent presentations and may also remit at certain ages. Accordingly, the ILAE position papers separately describe syndromes with onset in neonates and infants (up to 2 years of age), syndromes with onset in childhood, and syndromes that may begin at variable ages (meaning in both pediatric and adult patients). A separate position paper on idiopathic generalized epilepsies also is available [52]. Many syndromes are strongly correlated with a range of specific intellectual, psychiatric, and other comorbidities [51].

The syndromes are further subdivided into generalized, focal, or generalized and focal, based on seizure type(s), with a separate category for syndromes with developmental and epileptic encephalopathy (DEE) or progressive neurological deterioration [53]. The term DEE denotes an epilepsy associated with developmental impairment that may be due to both the underlying etiology and superimposed epileptic activity. Most DEEs present very early in life [53].

The 2017 epilepsies classification presents three levels of diagnosis. Where possible, a diagnosis at all three levels should be sought [51]. The first level of diagnosis is seizure type: focal, generalized, or unknown onset. In settings without access to EEG, video, and imaging studies, seizure type classification may be the maximum diagnostic level possible [51]. The second level of diagnosis is epilepsy type: focal, generalized, or unknown onset and a new category of "combined generalized and focal epilepsy." Many epilepsies will include multiple seizure types [51]. The third level of diagnosis is epilepsy syndrome—a cluster of features incorporating seizure types, EEG, and imaging features that tend to occur together [51].

Common epileptic syndromes include febrile epilepsy, childhood absence epilepsy, JME, and reflex epilepsies [54]. In total, the ILAE has identified more than 30 epileptic syndromes [54].

The patient's history and the witnesses' detailed account of the seizure are critical elements in treating any patient with epilepsy [4]. These reports are often the primary mechanism to assess seizure intensity, duration, and frequency. An accurate and detailed seizure description is only achieved by asking open and pertinent questions. A seizure diary, kept by the patient and/or his or her family, can provide very useful information.

The patient should be questioned regarding any significant medical history [4,55,56]:

The patient should also be questioned regarding any significant family history of epilepsy. In addition [4,56]:

Determining the patient's knowledge of the seizure is an important aspect of the history [4,55,56]:

The patient and family/witness should be questioned about the duration of the seizure, timing the active event in seconds [4,56]:

Any witness can provide substantial information regarding a seizure episode. The witness can describe the patient's level of consciousness and behavior. Furthermore, the witness can detail events related to the patient's muscle tone, injuries, state of confusion, residual paralysis, and alertness [4,56]. Fortunately, another individual often accompanies the patient with epilepsy due to imposed driving restrictions.

The patient's and/or witness's report of seizure activity is significant in caring for the person with epilepsy. These reports are often the primary mechanism to assess seizure intensity, duration, and frequency. This information often determines medication choices, dosage adjustments, and follow-up recommendations.

Patients and family members often inaccurately label the type of seizure experienced. Healthcare personnel should interpret a patient's description of the seizure in order to determine seizure type. Patients may state that they have "grand mals" when the seizures are actually tonic-clonic or focal seizures, including focal seizures that evolve bilaterally. Or, a patient may simplify the categorizations to "little" and "big," describing different manifestations of focal seizures. Often, patients have referred to their seizures with their individual terminology for years and renaming them is not helpful. A notation can be placed in the chart clarifying the patient's descriptions to assist all care providers to depict the seizures in a consistent and accurate manner.

A study conducted to determine seizure reporting to general practitioners has revealed that patients reported significantly more seizures on questionnaires completed anonymously, after visits to their doctors, than they reported during the office visits [57]. Patients may conceal seizure reporting because of the effect on various lifestyle patterns, including driving, employment, and leisure activity.

Patients and families should be encouraged to provide accurate and honest answers. A supportive environment should be provided to allow for candid and truthful discussions in order to provide the most applicable and beneficial care.

A comprehensive physical examination helps to determine the patient's health status, contributing factors, or secondary causes of epilepsy. The assessment should focus upon genetic diseases, neoplasms, infections, poisonings, and autoimmune diseases, including systemic lupus erythematosus. Characteristics of organ dysfunction, including hepatic, cardiac, pulmonary, and renal alterations, should also be evaluated. A general physical examination should be performed to exclude a non-neurologic cause of the seizure [56].

The diagnosis of epilepsy is based on several factors, with history as one of the most significant. A clinical history of seizures with concurrent EEG changes can usually establish the diagnosis of epilepsy. Signs or symptoms that may be most useful in the differentiation of epileptic seizures from other conditions include abrupt onset; altered or lost awareness (if not a focal seizure variant); brief duration; rapid recovery; and recurrent stereotypic episodes [9]. However, there are numerous disorders that mimic epilepsy. These disorders must be differentiated because they can be serious, life-threatening conditions that require intervention and treatment. Some conditions that must be ruled out in the differential diagnosis include syncope, hyperventilation syndrome, transient ischemic attack (TIA), migraine, and cataplexy [1,56].

Syncope can occur due to arrhythmia, cardiac disease, vasovagal response, and orthostatic hypotension [60]. Syncope can present with jerking movements and incontinence, which may confuse the diagnosis. Differentiating characteristics in syncope include light-headedness, weakness, hypotension, and nausea. In a simple "vasovagal faint," the person usually recovers immediately after becoming recumbent.

Hyperventilation is often diagnosed in young adults. The patient may exhibit carpopedal spasms or muscle cramping similar to epileptic twitches. The patient, however, will usually complain of shortness of breath with light-headedness [61]. These patients will also exhibit alterations in breathing that are dissimilar to those noted during an epileptic seizure.

TIAs usually present with paralysis, visual changes, aphasia, and sensory alterations. The patient is conscious during a TIA, although confusion may occur. Most symptoms of a TIA disappear within an hour, although they may persist for up to 24 hours [62].

A migraine can occur with an aura, although the aura associated with migraine is generally of a longer duration than a focal seizure. Cataplexy occurs in patients diagnosed with narcolepsy [60]. The sudden changes in movement and muscle tone noted during cataplexy could mimic seizures; however, the other clinical symptoms, including daytime sleep attacks, challenge this diagnosis.

There are other disorders that imitate the clinical picture of a seizure disorder. Metabolic and toxic disorders can occur in a number of settings. These situations include alcoholic blackouts, ingestion of hallucinogens or anticholinergics, sleep disorders, cardiovascular events, porphyria, movement disorders, and psychiatric disorders [63]. Some individuals will have a variety of independent, yet overlapping diagnoses. There may be a pathophysiologic and clinical correlation of migraine, epilepsy, and cerebral vascular disease in the same individual. One diagnosis does not automatically rule out other considerations in the same patient.

There are several diagnostic procedures that aid in the evaluation and management of individuals with suspected seizures or epilepsy. There are procedures available to evaluate brain wave activity, visualize brain structure, and explore the blood flow and function of specific regions of the brain. Each test is meaningful and helpful when applied in appropriate and unique situations. However, EEG and magnetic resonance imaging (MRI) are the primary tests utilized.

Magnetic Resonance Imaging

The American College of Radiologists asserts that magnetic resonance imaging of the head without contrast is the imaging modality of choice for the assessment of new-onset seizure not related to trauma in adults 18 to 40 years of age.

(https://acsearch.acr.org/docs/69479/Narrative Last Accessed: September 28, 2022)

Strength of Recommendation: Usually Appropriate

Imaging studies are essential to determine the anatomy, function, and possible structural abnormalities in the brain. Seizures may arise from specific areas or the general regions of anatomic abnormalities. MRI is the structural imaging tool of choice [2]. MRI uses strong magnetic fields and radiofrequency electromagnetic radiation to produce images of body structures without the use of x-rays or other ionizing radiation [68]. MRI is one of the most sensitive imaging tools to assess intracranial abnormalities, including tumors, arteriovenous malformations, infections, ischemia, cysts, atrophy, cerebrovascular accidents, and hemorrhage. The hippocampus and medial temporal lobe can be visualized and evaluated with MRI [66]. Assessment of these areas is an essential component of imaging studies, as alterations in this area are often helpful to localize an epileptogenic focus. The observation of mesial temporal sclerosis often correlates with the clinical findings of temporal focal seizures. Surgically treatable lesions, such as low-grade gliomas, cortical dysplasia, and cavernous angiomas, may be detectable by MRI but not by other imaging modalities [38,42,68]. Intravenous contrast media may be used to increase the sensitivity and specificity of the examination.

Most patients are able to undergo an MRI scan without any difficulties. Exceptions include those patients who are markedly obese, pregnant, unable to be in a supine position for approximately one hour, or unable to tolerate a confined area. A sedative, such as diazepam, is useful in many cases to mitigate the effects of claustrophobia in patients who are too uncomfortable to enter the apparatus [69].

To ensure a safe and successful MRI, patients must remove any items or substances that contain metallic (ferromagnetic) components, including jewelry, wallets, car keys, dentures, or pins. The patient must also forgo cosmetic use, as some brands contain ferromagnetic ingredients. Patients must not have any implanted devices, such as a vagus nerve stimulator, hearing aid, cerebral aneurysm clip, or cardiac pacemaker, which might be dislodged by the procedure. This also includes susceptible metal objects, including shrapnel or other metal fragments [69]. Titanium implants are not influenced by the procedure, and orthopedic implants that have been in place for long periods of time are also usually allowable.

During an initial evaluation of a patient, a comprehensive laboratory profile should be completed. The laboratory results can assist in determining an etiology for the patient's seizures and aid in treatment decisions. If a causative factor is discovered, treatment will be essential to correct the underlying disorder. Otherwise, the laboratory results are useful in ascertaining which AED will be the most opportune for the patient. Initial laboratory evaluations should include electrolytes, a comprehensive metabolic panel, complete blood count (CBC), erythrocyte sedimentation rate, blood urea nitrogen, creatinine, and liver function tests [66]. If the history is suggestive, then toxic screens for drugs, alcohol, and toxin levels, such as lead, may be useful. A lumbar puncture may be performed to help rule out an infectious etiology of a seizure. In addition, measuring the pressure of cerebral spinal fluid is useful in the diagnosis of a possible mass lesion. Laboratory analysis of the cerebral spinal fluid may also be of benefit [71,72].

Patients who are prescribed AEDs will often require additional laboratory testing. Depending on the medication, intermittent testing of liver function, CBC, and electrolytes may be required. Monitoring plasma blood levels of AEDs can be a useful tool to assist with the management of medication types and doses. Levels can be used to determine medication compliance, therapeutic failure, and adverse reactions. AED blood sampling should be completed at the same time for each patient, usually prior to the first dose of the day. When medication dosages are altered, the new dosage should be maintained until a steady state is achieved prior to obtaining levels [73]. Generally, four to six half-lives of the medication should be completed; for phenytoin, this time period is approximately 5 to 10 days [74]. Blood level evaluations are helpful in patient care but must always be correlated with the patient's clinical status. Patients may require a level of medication higher or lower than the stated "normal" levels. A therapeutic dose is one that controls the seizures with a minimum number of side effects, regardless of the numerical value of laboratory test results.

Seizures can begin at any age, but commonly arise before 20 years of age. Each year 25,000 to 40,000 children in the United States experience their first unprovoked seizure [75]. Children who experience seizures face unique challenges. Some children's seizures may be self-limiting and some experience no disease state, while other children develop devastating forms of epilepsy. These children's needs may vary considerably but often are related to developmental delays, depression, absence from school, and problems with their peers [76].

Children diagnosed with epilepsy will require regular office visits and evaluations. The administration of AEDs poses unique situations in children. Children grow rapidly and their weight changes, which requires alterations in medication doses. Children also have an increased metabolism and may require higher relative medication doses than those used in adults. A school-aged child may be able to assist in taking medications on their own with parental or school nurse supervision and aids such as a pillbox. AEDs may affect a child's academic performance and achievements. Interfering factors include side effects of medications, unrecognized seizures, alterations in brain function, and missed school days. Medications such as phenobarbital may make a child sleepy and may impair learning. Adjusting medication doses or timing of the medication may assist in the child's attentiveness and ability to concentrate [75].

Epilepsy affects approximately 300,000 elderly patients in the United States, which is the most rapidly growing population group with epilepsy [91]. Elderly patients with epilepsy may be difficult to manage. One of the primary concerns is that elderly patients are often prescribed multiple concomitant medications, which can predispose the patient to drug interactions and adverse effects. Another concern is that elderly individuals metabolize medications less effectively and often have an increased sensitivity to side effects. These side effects include fatigue, unsteadiness, and forgetfulness, which can lead to falls, broken bones, and a loss of independence [91]. Care should be taken to evaluate the patient and to provide therapies consistent with the patient's abilities and situation.

Women may experience epilepsy differently from men due to hormonal changes and the reproductive cycle. There is an unclear relationship between female hormones and neurologic functioning. Estrogen can stimulate and progesterone can inhibit some neurons that are involved in seizure activity [92]. Women have unique needs in regard to factors related to ovulation, reproduction, and menopause that can affect epilepsy [92]. Some women experience changes in seizure activity that coincide with hormonal fluctuations. During puberty, epileptic females may experience a decrease in seizure activity, while others may initially develop an epilepsy disorder at this time. Other women report a change in seizure patterns during ovulation or around the time of menstruation. Often, patients will report an increase in number or severity of seizures during the premenstrual days and the first few days of the menstrual cycle. This phenomenon is called catamenial epilepsy [92].

Temporal lobe epilepsy is associated with an increased likelihood of disorders, such as polycystic ovarian disease, amenorrhea, early menopause, and irregular menses [92]. The hypothalamus and pituitary gland control the regulation of gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin. Thyroid and adrenal corticoid hormones also affect ovulation and reproduction. The hormonal regulatory centers for these hormones are connected to the temporal lobe and, as a result, seizure disorders in this region may affect the regulation of these hormones. There is also evidence that some AEDs may disturb hormonal regulation, but their effects on fertility are not entirely clear [92]. Long-term use of some AEDs negatively affects bone health in women [92].

Preconception counseling is essential for all women with epilepsy who are of childbearing age. If the woman does not want children at the time of consultation, then contraceptive methods should be discussed that are acceptable to the individual. Some AEDs interfere with the metabolism of oral contraceptives, levonorgestrel implants, and medroxyprogesterone injections. When a liver enzyme-inducing medication, such as oxcarbazepine, phenytoin, carbamazepine, phenobarbital, primidone, or topiramate, is administered concomitantly with an oral contraceptive, the contraceptive will be metabolized more quickly and become less reliable [92]. Lamotrigine, levetiracetam, tiagabine, and gabapentin have no effect on the liver enzyme system and do not interfere with the effectiveness of hormonal contraception [92]. Whenever possible for women with epilepsy who are using hormonal contraception, an AED that does not enhance the liver enzyme system should be prescribed. These include valproate, felbamate, gabapentin, lamotrigine, levetiracetam, and tiagabine. If optimal seizure control requires use of an enzyme-inducing AED (i.e., carbamazepine, oxcarbazepine, phenytoin, barbiturates, or topiramate), a contraceptive agent should be prescribed that contains hormone dosages adequate to suppress ovulation. In addition, healthcare providers should recommend a barrier method of contraception [92]. Women should be educated about the reliability of each method, alternative methods, and when to notify a healthcare professional. Notification is essential when the patient experiences breakthrough bleeding, menstrual irregularities, changes in seizures, or other adverse effects.

Overall, there is a 2% to 3% risk of a woman having a child with an alteration at birth. The risk increases to 4% to 6% in women with epilepsy [93,94]. This increased risk is due to a number of factors, including genetics, seizures during pregnancy, and the use of AEDs. As with many medications, AEDs have the most devastating fetal effects during the first few weeks of pregnancy. Unfortunately, women are not always aware of the pregnancy during this time period. The risks of AEDs are starting to be understood, but the risk of having seizures during pregnancy is less clear. There is some evidence that seizures may cause abnormal uterine contractions that could account for the increase in miscarriage, stillbirth, and hemorrhage seen in women with epilepsy [95]. These issues must be discussed with women and their partners prior to conception.

When a woman expresses her desire to have children, certain considerations are made regarding medication choices and regimens. There must be an appropriate and individualized balance between the risk of medications and the risk of seizures. In the majority of cases, the risk of seizures outweighs the risks associated with the medications. All women should be counseled to notify their healthcare providers when they become pregnant. Women must be told to continue their medications as prescribed and not to stop or alter the medications on their own [96]. The Epilepsy Foundation has recommended that women take the following actions to increase their chances of successful pregnancy and long-term health [97]:

Women who take anticonvulsants and become pregnant are also encouraged to enroll in the AED Pregnancy Registry [98].

The risk of major congenital malformations in the offspring of women with epilepsy is possibly decreased by folic acid supplementation. The American Academy of Neurology and the American Epilepsy Society recommend that preconception folic acid supplementation in women with epilepsy be considered to reduce the risk of major congenital malformations.

(https://www.aan.com/Guidelines/home/GuidelineDetail/333 Last Accessed: September 28, 2022)

Strength of Recommendation: C (Possibly effective for the given condition in the specified population)

The addition of folic acid to the diet, especially in those women who lack adequate nutrition or are taking AEDs, may decrease the risk of abnormalities in the newborn. The patient should be provided with the reassurance that more than 90% of epileptic women who become pregnant give birth to healthy infants with no abnormalities (e.g., cleft lip, cleft palate, heart abnormalities, or spina bifida) [94]. This percentage is even higher if the pregnancy is planned in advance with the consultation of a neurologist; preconception adjustments, as needed, are made to AEDs; supplemental folic acid taken; and the woman receives early and ongoing prenatal care [92,94].

Data from multiple studies have demonstrated an increased risk to the unborn child with the use of valproate and suggested that it is not the best first choice for women of childbearing age. Overall, valproate and carbamazepine appear to pose the greatest risk of neurologic abnormalities [74]. However, when no other anticonvulsants work to control an individual's seizures, then the risk may be reduced by limiting the dose during pregnancy. The AAN and the American Epilepsy Society (AES) have recommended that women with epilepsy avoid taking valproate during pregnancy and that they also avoid taking more than one epilepsy drug at a time (i.e., polytherapy) during pregnancy if possible. Valproate use, and to a lesser extent polytherapy, have been linked to an increased risk for birth defects and an increased risk for developmental delay in children after exposure during pregnancy [74,92,99]. The FDA has issued a reminder to healthcare professionals about these risks, especially with exposure during the first 12 weeks of pregnancy [100]. Nevertheless, women taking any AED should not discontinue the drug on their own and should consult with their physician if they are, or may become, pregnant [92,99].

The pregnant epileptic woman will require early prenatal care and possible genetic counseling. Some neonates develop coagulation disorders that are related to vitamin K deficiency. These disorders are usually noted in mothers taking phenytoin, phenobarbital, and primidone throughout the pregnancy. Newborns exposed to AEDs routinely receive vitamin K at delivery, as do all newborns. However, the AAN has concluded that there is inadequate evidence to determine whether prenatal vitamin K supplementation in women with epilepsy reduces the risk of neonatal coagulation disorders [101].

Although AEDs may be found in breast milk, their presence does not preclude breastfeeding for most women. Primidone and levetiracetam transfer into breast milk in amounts that may be clinically important, but valproate, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts [74,101]. Caution with phenobarbital use has been recommended [74]. In some cases, infants of breastfeeding women experience somnolence or irritability, especially with phenobarbital. Supplemental bottle feedings may be recommended.

During menopause, seizure characteristics may change in women. Many women report an improvement in their condition, others state that the seizures worsen, and some report no change [92]. Hormonal replacement therapy must be carefully considered and balanced with other risk factors, such as cardiac disease, osteoporosis, uterine cancer, breast cancer, and the patient's epilepsy [92]. In general, patients receiving supplemental estrogen should also receive progesterone to assist with seizure control. More research is required to understand the complex issues related to women and epilepsy. Research should focus on these unique issues in regard to management, medications, and treatment [102].

Men with epilepsy may also experience cyclic or hormonal fluctuations in their seizure patterns. Fertility and reproductive changes affected by epilepsy in men are not well understood and appear to be multifactorial and common. Psychosocial complications associated with epilepsy may also affect reproductive health and sexuality [103]. Approximately one-third of men with epilepsy report having trouble obtaining and maintaining an erection [11]. Clinicians should investigate such problems, not only because of their multifactorial nature, but also because both patients and physicians often fail to recognize or may be reluctant to acknowledge them. This may be particularly true in men whose epilepsy had its onset before puberty, because they may lack subjective awareness about normal sexual response and function [103].

There is hope that the medications for erectile dysfunction may help with this problem; however, at this time there is insufficient evidence to make an estimate of any benefit. Medications (or surgery, in some cases) for erectile dysfunction surgery may be useful; some researchers have cautioned against concentrating only on hormone levels to explain sexual dysfunction and have encouraged that future studies include measures of quality of life, anxiety, and depression among men with epilepsy [103,104].

The utilization of AEDs is the mainstay of therapeutic options. The effectiveness of AEDs relies on the ability to classify the seizure type by its clinical presentation, history, and diagnostic test findings. It is important to know the correct seizure type, as some AEDs will be more effective or will exacerbate certain seizures or seizure syndromes (Table 3). Other factors to consider include patient age, gender, long-term goals, health history, drug interactions, potential side effects, and psychologic history. The goal of AEDs is to reduce or control seizure activity with no side effects, not to cure the disorder [105]. In general, focal seizures are more difficult to treat with medications than generalized seizures. AEDs allow approximately 70% of epileptic patients to achieve seizure control with minimum side effects. Another 20% to 30% can achieve good control with current medications, although some adverse effects may be experienced [106]. A patient's response to the first AED has been found to be an indicator of the success of any AED [107,108]. If a patient does not respond well with the first medication due to lack of efficacy, then it is likely that the patient may have refractory epilepsy [106]. However, if treatment failure is due to side effects or an idiosyncratic reaction, then alternative AEDs or other treatment options (e.g., surgery) may be more successful [106,107].

AEDs assist patients by stabilizing nerve cell membranes and preventing the spread of abnormal electrical discharges. Many of the medications require a therapeutic level of effectiveness to provide the best seizure control with minimum side effects. Treatment with medications usually focuses on using an adequate dose of a single medication (i.e., monotherapy) rather than smaller doses of several drugs. Monotherapy is the goal for most patients due to the benefits of improved drug compliance, reduced cost of medication and laboratory evaluations, lower risk of adverse effects, and lessened chance of drug interactions. Monotherapy successfully manages nearly 50% of epilepsy patients and is particularly desirable for certain special patient populations, such as women, the elderly, and patients with comorbid conditions [106,109,110,111]. Polytherapy offers no advantage over monotherapy for the majority of patients with epilepsy and may substantially increase the risk of AED toxicity and seizure aggravation. Polytherapy may be necessary, however, for patients who develop refractory epilepsy [34,110,111,112].

If the first AED that is attempted proves undesirable due to lack of efficacy (i.e., the patient fails to become seizure-free) or adverse effects, the first medication may be tapered off, while a second is slowly added [110,111,113]. When switching from one AED to another, choosing one with a different mechanism of action may increase the likelihood of a successful treatment response [111]. After several single medications have been used that are consistent with the patient's seizure type, polytherapy may be attempted. It is common for a refractory patient to require a daily regimen of two or three AEDs. Adequate treatment may take several weeks or months to become beneficial [110,111]. During treatment, healthcare providers should consider the possibility of patient noncompliance, incorrect diagnosis, and other factors that may contribute to the ineffectiveness of a medication choice [110].

Side effects are common with many AEDs (Table 4). These adverse effects include, but are not limited to, drowsiness, nausea, visual changes, and fatigue. Some adverse effects are related to the dose of the medications, while other effects, such as allergic-type reactions, occur regardless of the dose. With some medications, certain side effects are noted when a drug is first initiated or with a change in dosage. Depending on the type of side effect, it may abate with time. For example, dizziness, a common side effect with carbamazepine, often improves with continuation of the medication.

According to the American Academy of Neurology and the American Epilepsy Society, patients should be advised that their risk for antiepileptic drug adverse events ranges from 7% to 31% and that these adverse events are predominantly mild and reversible.

(https://www.aan.com/Guidelines/home/GetGuidelineContent/688 Last Accessed: September 28, 2022)

Strength of Recommendation/Level of Evidence: B (Probably useful based on at least randomized controlled study or two consistent cohort studies.)

Patient education is crucial to obtain medication adherence and provide optimum patient care. The patient should receive instruction on the type, dose, and potential side effects of each medication [111]. The patient should also understand that the medication is to be taken every day, on time, and as prescribed. Although brand and generic drugs are comprised of the same active compounds, their absorption may vary and patients should be cautioned not to interchange the medications. To avoid undesirable drug interactions, all professionals writing prescriptions, including dentists, should be aware of all medications a patient is taking. The patient should be informed that many medications interact with other CNS depressants, including alcohol. Patients should be requested to bring medication bottles with them at each visit.

As mentioned, monitoring of drug levels is an important aspect of anticonvulsant therapy [111]. Patients should be informed of the frequency and necessity of blood draws. Many AEDs have a common range of levels associated with the desired therapeutic effects with the least likelihood of adverse reactions. Occasionally, patients may benefit from a level outside the ranges and have intolerable side effects at low levels (Table 5). An overview of several specific medication dosages and indications is available in Table 6.

It must be remembered that treatment of seizures and epilepsy is accomplished on an individual basis with each patient. Appropriate drugs, doses, and side effects may vary with each individual [74,114,115].

As noted, AEDs represent the main therapeutic approach for patients with epilepsy. Other labeled indications include bipolar disorder, mania, neuralgia, migraine, and neuropathic pain. An increase in off-label use of AEDs has also been reported. This wide range of indications and common use in patients with or without psychiatric co-morbidities has raised questions about the safety of AEDs. In 2008, the FDA published a meta-analysis that included data from 199 placebo-controlled trials of 11 AEDs (carbamazepine, divalproex, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, and zonisamide) used either as monotherapy or as adjuvant therapy. The FDA found that patients receiving an AED had approximately twice the risk of suicidal behavior or ideation (0.43 per 100) compared with patients receiving placebo (0.22 per 100). As a result of the findings, the FDA required that the product labeling of the entire class of antiepileptics include a warning concerning the risk of suicidal thoughts and behavior. The agency also stated that patients, their caregivers, and their families be informed of these risks and advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm [74,116,117].

Although the FDA found that the results for individual drugs were generally consistent with the overall result, some researchers felt that this meta-analysis was not sufficiently large to fully investigate individual AEDs. Additional exploratory analysis of the risk of suicidal acts and combined suicidal acts or violent death associated with individual AEDs has suggested that the use of gabapentin, lamotrigine, oxcarbazepine, and tiagabine, compared with the use of topiramate, may be associated with an increased risk of suicidal acts or violent deaths [116,117].

Carbamazepine

The mechanism of action of carbamazepine is generally recognized to be the inhibition of nerve impulses by repressing sodium ion influx across cell membranes in the motor cortex. This medication is used for first-line therapy in the treatment of generalized tonic-clonic and focal seizures. There is no indication for the use of carbamazepine in absence or myoclonic seizures [74,119].

Carbamazepine treatment is initially started with a low dose and tapered upward to prevent the occurrence of adverse effects and to allow stabilization of drug levels. When discontinuing therapy, a down titration is recommended [119]. The primary side effects of carbamazepine are lethargy, dizziness, and GI side effects. A reduction in these side effects is often noted during the first few weeks of therapy. Other adverse effects include headache, ataxia, visual changes, mood alterations, and difficulty concentrating [74].

Idiosyncratic side effects include hepatitis, hyponatremia, skin photosensitivity, and systemic lupus erythematosus. The life-threatening side effects of carbamazepine include agranulocytosis, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS). The risk of TEN and SJS is highest in patients of Asian descent who have a genetic risk factor [74,119]. Patients will require monitoring of the CBC and for the appearance of a rash [74,105].

The National Institute for Health and Clinical Excellence recommends considering lamotrigine or levetiracetam as first-line monotherapy for children, young people, and adults with focal seizures.

(https://www.nice.org.uk/guidance/ng217 Last Accessed: September 28, 2022)

Strength of Recommendation: Expert Opinion/Consensus Statement

Most of the absorbed carbamazepine is metabolized to carbamazepine 10, 11 epoxide (CBZ-E) by the liver. The metabolism of carbamazepine changes with the duration of treatment, and after several weeks of dosing, the half-life is often reduced [74]. Metabolism occurs more rapidly in children than in adults [34,119]. Though clinical activity for the epoxide has been postulated, the significance of its activity with respect to the safety and efficacy of carbamazepine has not been established [119]. Monitoring of the parent drug and epoxide levels is important to evaluate the drug's metabolism and to provide the appropriate dose. Carbamazepine is an effective inducer of drug metabolism, and there are drug interactions with a variety of medications [74,105,119]. These interactions may raise or lower carbamazepine levels [74,119].

The absorption of carbamazepine can be slow and erratic, resulting in peak levels of the drug at various time intervals [74]. Tegretol XR, Equetro, and Carbatrol are long-acting forms of carbamazepine. Patients often have improved tolerance to side effects with the delayed release capsules and the improved steady state drug levels. Carbatrol is believed to have less variability in regard to the absorption of carbamazepine. Carbatrol is not effective and may have negative effects for generalized absence and myoclonic seizures.

Although surgical techniques have improved markedly over the past few years, epilepsy surgery is rarely considered a first-line treatment and is usually considered only after years of medication treatment. A surgical approach may be deliberated sooner if the patient's ability to function is hampered by frequent or severe seizures and a specific epileptogenic focus, such as mesial temporal sclerosis, is identified. Surgery for such well-defined syndromes has been shown to yield a better quality of life and reduced anxiety and depression within three months when compared with continued medical therapy [134]. Other focal lesions, including arteriovenous malformations, tumors, and areas of cerebral trauma, have also been successfully resected. The objective of a surgical approach is to obtain a significant decrease in seizure frequency, intensity, or duration with the least sequelae. As a result of new surgical techniques and new ways of identifying affected areas, more of these operations are being done than ever before and with greater success [114].

Intracranial surgery involves inherent risks; however, these risks are less than the risks of uncontrolled seizures. The morbidity and mortality of seizures include accidental injury; cognitive decline; sudden unexplained death in epilepsy (SUDEP); and psychologic, social, and vocational impairment. These factors suggest that continued medical therapy after failure to control seizures with aggressive trials of AEDs is not optimal treatment of certain forms of epilepsy [134].

The precise numbers and type of AEDs to try before recommending surgery remain unknown for the various epilepsy syndromes; however, the AAN, the American Association of Neurological Surgeons, and the AES have recommended the following practice parameters [134]:

As previously noted, a large percentage of patients continue to experience seizures despite treatment with medications. Studies of patients with new-onset seizures have shown that only 64% have seizure freedom by the time they try their third AED [3]. Thus, after three different AEDs have failed to control seizures, more than 35% of patients continue to have seizures. Therefore, the decision to proceed with surgery should include consideration of both the chance of seizure freedom with additional AED trials and the adverse long-term effects of uncontrolled seizures [134].

While an estimated 60,000 people are candidates for surgery for epilepsy, not all patients are eligible [135]. For example, those with significant medical problems or progressive neurologic disorders are rarely considered surgical candidates. Several diagnostic and prognostic procedures are available to determine an individual's suitability for surgery. The presurgical testing commonly includes the patient's seizure history, a physical examination, laboratory tests, social circumstances, and simultaneous video/EEG monitoring. An MRI, PET, SPECT, neuropsychologic tests, sphenoidal electrodes, and an intracarotid sodium amobarbital test are also commonly used screening methods [134].

Simultaneous video/EEG monitoring may continue for several days to several weeks, depending on the frequency of the patient's seizures. As mentioned, sphenoidal electrodes are inserted through the skin above the jaw and assist with locating seizure activity in the temporal lobe. The goal of this monitoring procedure is to determine the patient's seizure type and location of seizure onset and to evaluate the position of vital areas for speech and memory. It is important to record sufficient numbers of the patient's typical seizures to obtain the most accurate data possible [134]. The patient is kept in a controlled environment in which seizures may occur with consistent monitoring and with the oversight of experienced personnel. The patient's AEDs are usually tapered, and aggravating factors are instituted. Aggravating factors may include sleep deprivation, hyperventilation, or physical exertion.

Neuropsychologic (or neurocognitive) tests analyze a patient's memory, attention, concentration, language, motor skills, intelligence quotient (IQ), and other problem-solving abilities. Epilepsy surgical candidates routinely undergo extensive neuropsychologic testing [134]. These tests are lengthy and may take five or more hours to complete, but they can assist in the localization of a lesion. Testing also gives the healthcare team a better understanding of the patient and how the patient may progress through the surgical process to rehabilitation [134].

The intracarotid sodium amobarbital test, often referred to as the Wada test, combines neuroimaging and neuropsychologic testing methods. The purpose of this test is to determine areas of the brain that are important in speech, thinking, and memory. Although this continues to be a use of the Wada test, functional MRI for language now provides a noninvasive way to more accurately lateralize and localize language functioning [134]. The information derived from the Wada test helps the surgical team determine a proper surgical approach and ascertain any anticipated surgical complications. The patient is conscious throughout the procedure, during which carotid angiography is performed, usually through a femoral approach. One hemisphere of the brain is anesthetized for several minutes with sodium amobarbital or a similar barbiturate. After the injection, the patient is tested for speech and memory. This consists of reading words, identifying objects or pictures, and answering questions. The patient is then asked to remember what is shown. Arm and hand strength is also tested. The entire side of the body contralateral to the injection site will be momentarily paralyzed. Either one or both sides may be tested in the same manner. A recall of 75% of the items presented during anesthetization is evidence that the contralateral hemisphere should be able to support memory after surgery. Insufficient recall is evidence that the patient may experience significant memory difficulties postoperatively [134]. If additional information is required, a second hospital admission may be necessary for the surgical placement of epidural or subdural electrodes directly onto the surface of the brain. This procedure is generally reserved for the most difficult cases [134]. Depth electrodes, fine wires positioned directly into the deep brain matter, may also be placed. These invasive electrodes are capable of transmitting seizure information that is not detectable by a scalp electrode. While the invasive electrodes are placed, functional mapping may be completed. Functional mapping involves stimulation of the electrodes while the patient is performing certain tasks. These interventions assist in eliciting the seizure focus and determining the involvement of important brain functions [134].

After presurgical testing is complete, further consultations should occur to determine the patient's eligibility for surgery. In this stage, the patient is evaluated to determine the potential benefits versus the risks of a surgical procedure. There are many important questions to consider, such as whether the seizures impair functioning, the severity of the toxicities of the medications, and whether the seizures or the sequelae are harmful to the patient. Finally, the patient's quality of life issues should be addressed.

There are several commonly accepted procedures for the removal of a focal epileptogenic focus. Open surgeries include lobectomy, hemispherectomy, corpus callosotomy, and multiple subpial transection [134]. The use of radiation therapy to ablate the area of abnormality has been increasing in popularity and is available in many medical centers. A linear accelerator, widely known as the gamma knife, is commonly used as a radiation source [136]. The end result of all of these procedures is the interruption of seizure pathways or the removal of the seizure focus.

The vagus nerve stimulator, first approved by the FDA in 1997, was the first successful medical device for patients with uncontrolled focal seizures [3]. Jacob Zabara, a biophysicist, discovered that breathing techniques could stimulate the vagus nerve and decrease muscular contractions in the abdomen. Because the vagus nerve has an effect on the brainstem, hypothalamus, hippocampus, and amygdala, as well as innervating several organs, Zabara postulated that vagus stimulation could decrease seizures [141].

The stimulator is an implanted device, similar to a cardiac pacemaker, that is connected to the vagus nerve in the neck and stimulates the nerve with electrical impulses. The device is programmed to send electrical discharges at specific intervals automatically and periodically throughout the day [3]. The device is adjusted according to each patient's individual requirements and tolerance. The stimulator can be programmed externally by the attending physician or controlled, if necessary, by the patient with the use of a handheld magnet.

On average, this stimulation reduces seizures by approximately 20% to 40%. Patients usually cannot stop taking epilepsy medication because of the stimulator, but they often experience fewer seizures and they may be able to reduce the dose of their medication [3]. Not all patients are candidates for the device, and the device is approved for use in adults and adolescents only. The stimulator is used as an adjunctive therapy to medications and surgery, not as a first-line consideration. The most common adverse effects reported are hoarseness, alterations in speech, ear pain, cough, shortness of breath, nausea, and throat discomfort. Adjusting the amount of stimulation may eliminate most side effects, although the hoarseness typically persists [3]. Most patients consider the adverse effects to be tolerable.

The responsive neurostimulation (RNS) system is an adjunctive treatment for refractory epilepsy. It received FDA approval in 2013 for adults 18 years of age and older; in 2017, this was expanded to include patients 4 years of age and older [3,142,181]. The RNS is an implanted device that records and analyzes the patient's EEG and applies targeted stimulation (e.g., electrical stimulation, fast-acting drug) to prevent the seizure from occurring [3,143,144]. Controlled clinical trials have demonstrated that the RNS system reduces the frequency of disabling seizures, is well tolerated, and acceptably safe [145].

Deep brain stimulation (DBS) is the direct implantation of electrical stimulators in the basal ganglia (e.g., anterior thalamic nuclei) or the hippocampus in an attempt to control seizures in patients with refractory epilepsy. This treatment is FDA approved for use in various disorders, including essential tremor, dystonia, Parkinson disease, and obsessive-compulsive disorder. In 2018, the Medtronic DBS system received FDA approval to expand the indications to include use in adults with medically refractory focal epilepsy. The DBS system has demonstrated safety and effectiveness for patients who average six or more seizures per month over the three most recent months prior to DBS implant (with no more than 30 days between seizures). The system has not been evaluated in patients with less frequent seizures [143,146,147,148]. Serious adverse effects include brain hemorrhage, paresthesias, surgical site infection, and implant site pain [144]. DBS also is approved for refractory epilepsy in Europe, Canada, Australia, and Taiwan, and several trials have shown that the treatment is effective for patients with pharmacoresistant epilepsy (50% to 70% reduction of seizures, and 10% of patients seizure-free after several years) [144]. In 2020, the FDA approved a "new-era" DBS device called Percept. This device can chronically capture and record brain signals while delivering therapy to patients [149].

Researchers are also studying whether transcranial magnetic stimulation (TMS), a procedure that uses a strong magnet held outside the head to influence brain activity, may reduce seizures. In addition, work is being done on a device that can analyze an EEG and automatically deliver a dose of an AED in time to abort a seizure [3,114].

Psychologic interventions are important for the patient with psychogenic pseudoseizures. Patients will require counseling and support throughout this process. Psychogenic pseudoseizures often develop as a defense mechanism in response to difficult situations. If this coping strategy is challenged, patients may feel depressed, angry, and vulnerable. Extreme sensitivity and caution are required to achieve a positive outcome for the patient [64]. Prior to a definitive diagnosis, patients may be prescribed AEDs. The medication may continue until psychologic counseling is instituted, after which they are tapered off. A firm schedule of follow-up visits should be established. While the diagnosis of psychogenic pseudoseizures is as real as a diagnosis of epileptic seizures, the etiology, pathophysiology, and treatment are very different. Patients who have documented epileptic seizures may concurrently have psychogenic pseudoseizures. These patients will require psychologic intervention as well as care for the epilepsy [64].

Patients and families often seek alternative treatments in order to manage epilepsy naturally or if other treatment methods have been unsuccessful. The ketogenic diet is an alternative approach to standard medications and epilepsy care. It has been so widely recommended that it is becoming a mainstream form of therapy. Some assertions in the lay literature have suggested that vitamin E and selenium are helpful for some kinds of seizures; however, these claims have not been supported by scientific research.

Most individuals who develop epilepsy have a high likelihood of achieving resolution. Epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but who are past the applicable age, or those who have remained seizure-free for 10 years, with no seizure medications for at least the last 5 years [5]. Frequency, type, and number of seizures are important predictors of outcome [156]. Approximately 60% of patients with epilepsy will achieve a remission during the first year of therapy [157]. Another 15% will achieve a remission at a later time, after treatments have been instituted for a number of years. The remaining 25% will develop intractable epilepsy despite treatment. Patients with underlying neurologic disorders, such as multiple sclerosis and cerebrovascular disease, tend to have epilepsy that is more difficult to control. Patients should continue with regular office visits because seizure disorders may change with age in an unpredictable manner. Some seizures may be outgrown, while others worsen with time. Some patients improve for a period of years and then worsen. It is hoped that some of the newer modalities, including surgery and electrical stimulators, will have a synergistic effect with the AEDs and improve prognosis.

There are many misleading and inappropriate concepts about how to care for a person who is having a seizure. It is important for all healthcare professionals to know the basic tenets of care and to teach as many people as possible the proper way to handle a patient having a seizure.

The first rule is to "do no harm." Many individuals witnessing a seizure will try to restrict movement or otherwise restrain the patient. This may cause more harm than good. Bystanders and professionals are encouraged to simply take steps to keep the person safe [158]. For a person who is having a focal or nonconvulsive seizure, this merely requires guiding the individual away from a source of danger, such as a busy highway, steep stairway, or hot stove. In general, it is best to gently guide the person, as grabbing or holding may cause a struggle and aggravate the situation. Speak to the individual in a calm and reassuring way, and stay with him or her until the episode is over, especially if there is a period of unconsciousness [158].

When assisting a person who is having a generalized tonic-clonic seizure, it is vital to remember to keep calm and reassure others in the vicinity that there is no need to interfere. However, bystanders can assist in removing any sharp or dangerous objects in the immediate area. Loosening a patient's tie or any other object that may cause impairment to respiration may also be helpful. Removing loose dentures or food that is expelled from the mouth has been recommended, but forceful removal or shoving an object into the mouth may cause injury and is contraindicated [158]. Placing something soft and flat under the individual's head may prevent an injury, and turning the victim gently onto his or her side can help to clear the airway and avoid aspiration. There is no need for artificial respiration except in the very rare cases when respiration ceases and does not resume after the seizure ends. If in a care center, supplemental oxygen should be available and provided if indicated. The individual should not be left alone until the seizure ends naturally. One should be prepared to offer assistance to a possibly confused or somnolent postictal individual when the seizure activity ceases [158].

Timing the length of the seizure can provide useful information for the patient's future management. It would also be helpful to assess the patient's breathing and determine if there are any apneic periods [158].

Status epilepticus, or status, is defined as uninterrupted seizure activity or frequent succession of seizure activity. The time variable for status varies greatly depending upon the sources cited. In general, a patient is considered to be in status if a single seizure continues for more than 15 minutes or if there is a rapid succession of seizures lasting more than 30 minutes. Statistics support the notion that after about 30 minutes of seizures, mortality takes a robust leap [160,161]. However, the Epilepsy Foundation has advised that parents and the public call for emergency assistance when a convulsion continues for more than five minutes without stopping. The Foundation's Working Group on Status Epilepticus has recommended that emergency room physicians treat as status epilepticus if seizure activity has continued for more than five minutes [161,162,163].

Convulsive status epilepticus involves tonic-clonic seizures and is a medical emergency [161]. An estimated 55,000 deaths and thousands more instances of brain damage per year follow episodes of status [162]. The majority of these episodes occur in people who do not have epilepsy but have other acute medical illnesses, such as brain tumors or infections, craniocerebral trauma, or cerebrovascular disease. Ingestion of cocaine or other illegal drugs and toxic or metabolic disorders may also trigger a status episode.

Nonconvulsive refers to absence or long or repeated absence or focal impaired awareness seizures. Nonconvulsive status can present in various ways, including loss of speech, automatisms, and alteration of consciousness [161]. Nonconvulsive status seizures are harder to recognize than convulsive status seizures. Symptoms are more subtle, and distinguishing seizure symptoms from the recovery period is difficult [161]. While not generally viewed as being as damaging as convulsive status, nonconvulsive status involves repeated excessive electrical discharges in the brain and should also receive prompt treatment [162]. The most dangerous form is the tonic-clonic type. Cerebral complications occur from high metabolic demands, changes in calcium influx, brain edema, acidosis, hyperthermia, hypoglycemia, hypotension, prolonged autonomic dysfunction, hypoxia, arrhythmia, acidemia, aspiration, and ultimately, brain damage.

In 2016, the American Epilepsy Society (AES) issued new guidelines for the treatment of status epilepticus, which provide a time-dependent treatment algorithm consisting of four phases [164]. The first or "stabilization phase" occurs in the first five minutes of seizure activity and includes standard initial first aid interventions for seizures [164]. As with any emergency situation, the first priority is the maintenance of a clear airway. The patient sustains a rapid depletion of oxygen and other nutrients during status. Often, the individual is intubated to assist with oxygenation and the prevention of aspiration. The patient will usually require supplemental oxygen. Continuous assessment of all vital functions and neurologic status is necessary. Cardiac monitoring is required to identify dysrhythmias and to allow for appropriate intervention. The patient should be protected from injury and provided a safe environment with close supervision. Laboratory evaluations should be completed to assess AED levels and to check for any metabolic changes. The patient may require additional glucose, which is administered intravenously, to meet increased metabolic requirements. AEDs may be prescribed for intravenous injection and infusion [84,161,164].

Interventions for the initial therapy phase (minutes 5 to 20 of seizure activity) include a benzodiazepine (specifically IM midazolam, IV lorazepam, or IV diazepam). Although use of IM midazolam for status epilepticus is off-label, the AES guideline recommends it as the drug of choice when IM administration is necessary for emergent control [74,164]. Diazepam was once considered the drug of choice for the immediate treatment of status epilepticus; however, lorazepam has emerged as the preferred benzodiazepine for acute management of status epilepticus [84,164,165]. Lorazepam is less lipid-soluble than diazepam, with a distribution half-life of two to three hours versus 15 minutes for diazepam, providing a longer duration of clinical effect [165]. The anticonvulsant effects of lorazepam last 6 to 12 hours, and the typical dose ranges from 4–8 mg. This agent also has a broad spectrum of efficacy, terminating seizures in 75% to 80% of cases. Its primary adverse effect (respiratory depression) is identical to that of diazepam [84].

Interventions for the second therapy phase (20 to 40 minutes) include valproic acid, levetiracetam, and fosphenytoin. IV phenobarbital is a reasonable alternative if none of these recommended therapies are available [164]. Use of both valproic acid and levetiracetam for status epilepticus is off-label. However, the AES guideline recommends they be considered for use in urgent control of status epilepticus in adults [74,164].

Phenytoin is one of the most effective drugs for treating acute seizures and status epilepticus. The main advantage of phenytoin is the lack of a sedating effect. However, a number of potentially serious adverse effects, such as arrhythmias and hypotension, may occur. These effects may be associated with a more rapid rate of administration and the propylene glycol vehicle used as its diluent. In addition, local irritation, phlebitis, and dizziness may accompany intravenous administration [84].

The American College of Emergency Physicians recommends the administration of an additional antiepileptic medication in patients with refractory status epilepticus who have failed treatment with benzodiazepines.

(https://www.acep.org/globalassets/new-pdfs/clinical-policies/seizures-2014-final.pdf Last Accessed: September 28, 2022)

Strength of Recommendation: A (Generally accepted principles for patient care that reflect a high degree of clinical certainty)

Fosphenytoin was approved by the FDA in 1986 for treatment of status epilepticus. It is converted to phenytoin within 8 to 15 minutes. It is metabolized by the liver and has a half-life of 14 hours. It may be infused at a rate three times faster than that of intravenous phenytoin. However, adverse effects unique to fosphenytoin include perineal paresthesias and pruritus, both related to the higher rates of administration [74]. Although fosphenytoin represents an improvement over traditional phenytoin, it is expensive and some hospital formulary committees are unwilling to pay the difference [84]. Insufficient data exist about the comparative efficacy of phenytoin and fosphenytoin. When both are available, fosphenytoin is preferred based on tolerability, but phenytoin is an acceptable alternative [164].

The third therapy phase begins when seizure duration reaches 40 minutes (40 to 60 minutes). Although the AES guideline indicates that "there is no clear evidence to guide therapy in this phase," treatment considerations should include repeating second-line therapy or anesthetic doses of either thiopental, midazolam, pentobarbital, or propofol (all with continuous EEG monitoring) [164].

The patient's family members will require support and education during this time. When the patient is stabilized, the family members may be helpful in assessing the cause of the patient's status epilepticus and in finding solutions for the prevention of future events. The most prevalent cause of status epilepticus in epileptic patients is failure to comply with AEDs [162].

Patients with epilepsy have a mortality rate that is higher than the average population. Mortality may occur due to the etiology of epilepsy, which may include a malignant brain mass or a genetic abnormality. Death can also result from a seizure or a complication of a seizure. As noted, patients who develop status epilepticus may not recover. Other patients may have serious injuries or accidents that may lead to death, including falls or burns.

The most common epilepsy-related category of death is SUDEP, accounting for up to one-fifth of epilepsy deaths. SUDEP seems to occur more commonly during sleep, and it preferentially affects young adults with medically intractable epilepsy (especially tonic-clonic seizures). The bulk of evidence supports the concept that patients with uncontrolled seizures are at greatest risk for SUDEP. High seizure frequency and polytherapy also seem to be risk factors. Evidence for many other risk factors is conflicting. The most commonly suggested mechanisms for SUDEP are cardiac abnormalities and apnea, but the cause of SUDEP remains unknown [166,167,168].

Injuries are the primary complication of seizures. Patients with epilepsy often cause harm to themselves by biting their tongues or falling down and hitting a piece of furniture. As noted, the patient should be safeguarded from injuries and falls. Injury prevention is a key aspect of patient education and the maintenance of quality of life. The patient and family should be instructed on constructive methods of safety planning without being overburdened with unnecessary restraints and concern. If possible, the environment should be altered during a seizure rather than restraining the patient. A helmet may be a reliable alternative to provide a protective environment [171].

At home, the patient should evaluate the living situation. General household safety precautions include applying thick carpeting, padding sharp objects, avoiding lighting of fires, and obtaining automatic shut off switches for space heaters, curling irons, and irons. The patient should be informed that smoking is not recommended and certainly not permitted in bed. Bathroom safety measures include setting the water temperature below 120 degrees, using a hand-held shower while seated in the bathtub, installing padded carpet in the bathroom, and preventing the bathroom door from locking. The kitchen can be a perilous environment, and cooking can be especially dangerous for the individual who experiences a change in consciousness. Patients should be cautioned about the risk of falling onto a hot stove or leaving the heating elements and oven on. Kitchen safety measures include the use of plastic cups, plates, and cooking utensils, cooking on the back burners of the stove, using a microwave oven, and sliding containers on the counter top rather than picking them up [171].

Recreational activities pose a unique challenge for many active epileptic patients. Most individual sports are considered acceptable, with the exception of scuba diving, parachuting, or activities involving a motorized vehicle. Patients are generally advised that they may participate in basketball and baseball. Football and boxing are often prohibited. If indicated, a mask worn over the face or a helmet may be necessary and helpful during potentially dangerous activities. To improve their safety during recreational activities, patients should consider taking frequent breaks, exercising on soft surfaces, wearing head protection, and always taking along a companion [171].

Health promotion of individuals with epilepsy includes the management and reduction of seizure activity. The patient should be instructed to obtain adequate rest, limit alcohol, reduce stress, eat a healthy diet, and exercise. Patients susceptible to the effects of caffeine and aspartame should avoid these products. These interventions assist in the patient's overall well-being, prevent other disease states, and assist in seizure control [171]. Any precipitating situations that trigger seizure activity, such as flickering lights, should be identified and avoided. An accurate and comprehensive seizure diary may assist with revealing these factors. Patients should also be guided with regard to medication compliance and the necessity of follow-up visits. The patient and family members should be provided with appropriate resources, including information on the local chapters of epilepsy support groups.

Genetic epilepsies are not preventable. However, there are multiple avenues in which epilepsy can be prevented in the general population [172]. Prevention can occur before birth with improved prenatal care. Folic acid supplementation should occur in women of childbearing age prior to conception to prevent neural tube defects. The current recommended allowance of folic acid for nonpregnant individuals is 0.4 mg/day [173]. During pregnancy, care should be taken to avoid maternal systemic illness and infection, which can affect the developing fetus's CNS. A reduction in the number of early teenage pregnancies may decrease the incidence of premature and/or low-birth-weight infants and maternal infections. Improved perinatal care in the labor and delivery area may also decrease fetal trauma and hypoxia [1,3,4,92,172].

High fevers in children, especially in those susceptible to seizures, should be monitored and treated appropriately. Parents or caregivers of small children should be instructed in how to take an accurate temperature, based on the child's age. Parents should also be instructed about the significance of a fever and how to intervene when necessary; it is important that they understand when to call a healthcare professional regarding an elevated temperature and when to treat the child with antipyretic medications [4,27,77,172].

The prevention of childhood infection and toxic ingestions is crucial in averting the development of epilepsy. Meningitis, viral encephalitis, measles, mumps, and diphtheria can be minimized through appropriate immunization of children and adults. The prevention of toxic poisonings through screening and safety measures is essential. Lead poisoning continues to be problematic in many older homes [4,35].

Another area that may minimize the incidence of epilepsy is the reduction of motor vehicle accidents and the prevention of trauma. Traumatic injuries can occur through a variety of accidents and abuse. The utilization of safety belts and restraint devices in all motorized vehicles is essential for children and adults. Settings in which there is a potential for gunshot wounds should also be avoided to prevent the occurrence of head injuries and the subsequent development of epilepsy. Practicing safety during sporting activities is also essential. The prevention of abuse is vital in the reduction of head trauma-related epilepsy. Workplace injuries should be reviewed and reduced. Lastly, the prevention of substance abuse and the use of illicit drugs will assist in the reduction in the incidence of epilepsy [3,4,11,29,35].

Communication with patients regarding prevention and education is a vital aspect of caring for patients with seizure disorders or epilepsy. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Frequently, this may be easier said than done, as there may be institutional and/or patient barriers.

In a multicultural setting, interpreters are a valuable resource to help bridge the communication and cultural gaps between patients and practitioners. Interpreters are more than passive agents who translate and transmit information from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, interpreters serve as cultural brokers who ultimately enhance the clinical encounter. When providing care for patients for whom English is a second language, the consideration of the use of an interpreter and/or patient education materials in their native language may improve patient understanding and outcomes.

For individuals with epilepsy, the safe operation of a motor vehicle is a complex issue. The caregiver must try to achieve a balance between providing the best care to the patient and providing the patient with the autonomy and freedom that often coincides with driving. Safety must be the highest priority for the patient and for other individuals. This issue is further complicated by a variety of state statutes and regulations.

A helpful reference concerning driving restrictions in each state is available from the Epilepsy Foundation [174]. Each state has specific requirements for obtaining a driver's license and restrictions for persons with certain medical conditions (Table 7). Laws change, however, and each healthcare professional and patient should be aware of the current laws governing the state in which they practice and reside.

Patients with epilepsy face unique challenges. For many individuals with epilepsy, a perceived stigma creates diverse psychosocial issues [172,175,176]. A seizure may be referred to as a "fit" or an "attack," and there are corresponding bizarre interpretations of this phenomenon. Historically, seizures have been associated with supernatural powers, demonic possession, and insanity [3,42]. Society places value on self-control, conformity, and independence, all of which may be inhibited by a patient's epilepsy. There is confusion on the part of many individuals when a person has a seizure. Observers and the police may consider the individual drunk, disorderly, or mentally ill. The patient may be institutionalized or jailed.

Patients with active seizures frequently experience low self-esteem, resulting from perceptions of being less competent and less healthy than others [175,176]. The unpredictability of seizures, feelings of lack of control and helplessness, and the adverse effects of the medication regimen contribute to a disruption in the patient's sense of well-being [175,177]. Unfortunately, the majority of these psychologic alterations are not assessed by the general practitioner.

Patients with uncontrolled epilepsy are at greater risk of feelings of anxiety, depression, and stigmatization than those with less frequent seizures [176]. Frequent seizures impact employment and driving, which have a significant effect on self-esteem and feelings of isolation [172]. Unemployment among people with uncontrolled epilepsy has been found to be higher by as much as 50% in developed countries [57,175]. People with epilepsy have a higher prevalence of learning disabilities and memory problems, often caused by comorbid conditions such as brain damage. Children are exceptionally vulnerable to the negative impact on social and intellectual development. Attention deficits occur during seizures, especially during absence seizures in school-aged children. Children with epilepsy require medical care and AEDs that often affect academic and personal performance. The side effects of AEDs, such as drowsiness and short attention span, may affect educational achievement and are commonly exacerbated by polytherapy [57,175].

Healthcare personnel can help patients identify people who may be supportive and to whom they may explain the seizures and treatment. They may also help patients focus on positive aspects of life, rather than limitations. Appropriate referrals to an epilepsy specialist nurse, psychologist, psychiatrist, or community worker may be indicated. The community worker can provide support, be an informed and empathetic listener, alleviate fear of the unknown, encourage compliance, and provide information to the patient and the patient's family [175]. The interdisciplinary healthcare team should anticipate and provide solutions for common social issues, difficulty with self-image, frightening experiences, loss of control, and difficulty with independence. Essentially, all members of the team may be vital links to assist each individual to adjust to their personal limitations and difficulties. Lifestyle adjustments should be considered without unnecessarily inhibiting the patient's activities and routines.